RESTORATION OF SEVERELY DEPLETED FEMORAL TRABECULAR BONE IN OVARIECTOMIZED RATS BY PARATHYROID HORMONE-(1-34)

It is commonly believed that the parathyroid hormone's (PTH's) main fu nction in bone is to stimulate osteoclastic resorption. However, inter mittent injections of small doses of PTH holoprotein, but more often i ts bioactive hPTH-(1-34) fragment, have been shown to stimulate bone g rowth in animals and humans through their ability to stimulate adenyly l cyclase and not their ability to independently activate a protein ki nases-C stimulating mechanism. This anabolic action suggests that PTH might be an effective therapeutic for osteoporosis. If so, the hormone must be able to restore severely depleted trabecular bone, and the go al of this study was to find out if it can. To do this, we started a m ultiweek program of daily subcutaneous injections of 0.8 nmoles of hPT H-(1-34)/100 g body weight into rats at 4, 8, or 16 weeks after ovarie ctomy (OVX) and the increasingly severe selective loss of trabecular b one. These injections strongly stimulated femoral trabecular bone to g row and mineralize at the same rate regardless of how much of it had b een lost before the injections were started. Thus, the progressively d epleting trabecular bone in the femurs of OVX rats does not lose its a nabolic responsiveness to PTH. This finding is another indication of t he likelihood of small, adenylyl cyclase-stimulating PTH fragments bei ng effective therapeutics for osteoporosis.